Plos One
-
Comparative Study
The clinical utility of fMRI for identifying covert awareness in the vegetative state: a comparison of sensitivity between 3T and 1.5T.
In the last few years, mental imagery fMRI paradigms have been used successfully to identify covert command-following and awareness in some patients who are thought to be entirely vegetative. However, to date there is only evidence supporting their use at magnetic fields of 3T, which limits their applicability in clinical settings where lower field strengths are typically used. ⋯ We were able to successfully detect brain activity showing command-following in most participants at both 3T and 1.5T, with similar reliability. These results demonstrate that fMRI assessment of covert awareness is clinically viable and therefore justify a broader use of these methods in standard assessments in severely brain injured patients.
-
Case Reports
Megalencephaly syndromes: exome pipeline strategies for detecting low-level mosaic mutations.
Two megalencephaly (MEG) syndromes, megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyriapolydactyly-hydrocephalus (MPPH), have recently been defined on the basis of physical and neuroimaging features. Subsequently, exome sequencing of ten MEG cases identified de-novo postzygotic mutations in PIK3CA which cause MCAP and de-novo mutations in AKT and PIK3R2 which cause MPPH. Here we present findings from exome sequencing three unrelated megalencephaly patients which identified a causal PIK3CA mutation in two cases and a causal PIK3R2 mutation in the third case. ⋯ In addition, the PIK3CA mutation in one of our patients could not be detected using standard exome analysis because the mutation was observed at a low frequency consistent with somatic mosaicism. We have therefore investigated several alternative methods of exome analysis and demonstrate that alteration of the initial allele frequency spectrum (AFS), used as a prior for variant calling in samtools, had the greatest power to detect variants with low mutant allele frequencies in our 3 MEG exomes and in simulated data. We therefore recommend non-default settings of the AFS in combination with stringent quality control when searching for causal mutation(s) that could have low levels of mutant reads due to post-zygotic mutation.
-
Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. ⋯ Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.
-
The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. ⋯ Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.
-
Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas). ⋯ GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.